For a long time, clinicians have had the impression that women exposed to severe stress during pregnancy are at greater risk to produce children with developmental difficulties. Although studies of the effects of prenatal stress in human offspring are very important, the necessary controlled prospective studies in human subjects are difficult or impossible to perform. Animal models provide an alternative approach. Studies in nonhuman vertebrate species have demonstrated that events occurring prenatally produce long-lasting effects of the development of brain and behavioral system. Our laboratory recently demonstrated that when pregnant rats are exposed to repeated inescapable tail shock treatments they produce offspring with increased ACTH and corticosterone concentrations. These offspring also differ behaviroally form offspring on nonstressed mothers in that they do not develop an analgesic response to stress. The proposed studies will be performed in 2 parts. Studies in Part 1 will completely characterize HPA function in prenatally stressed rat pups. Specific experiments will be performed to assess mechanisms underlying activation and inhibition of the HPA system. Studies in Part 2 will assess factors involved in transmitting the effects of prenatal stress from mother to offspring. Emphasis will be placed on characterizing fetal and maternal hormonal changes induced by prenatal stress as well as examining the effects of the postnatal rearing environment. An additional focus of studies in Part 2 will be to test the hypothesis that prenatal stress-induced alterations in glucocorticoids play an important role in HPA and behavioral alterations in offspring. These studies will establish important principles regarding the mediation of the effects of prenatal stress on the development of the HPA system and stress related behavior in offspring. Ultimately such principles will aid in our understanding of the effects of prenatal stress on human development.